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The RAS/mitogen activated protein (MAP) kinase pathway in melanoma biology and therapeutics

Authors Abel D Jarell, Donald Lawrence, Hensin Tsao

Published 15 February 2008 Volume 2007:1(4) Pages 407—414

Abel D Jarell1, Donald Lawrence2, Hensin Tsao1,2,3

1Department of Dermatology; 2MGH Cancer Center, and 3Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Abstract: An effective treatment for metastatic melanoma remains one of the most elusive goals in all of oncology. Several generations of therapeutic trials have yet to yield any agents that can significantly prolong survival for widespread disease. Despite this disheartening history, our understanding of the biology and molecular genetics of melanoma hold the promise of a new era of molecular targets. One pathway that appears to be universally activated in and critically needed for melanoma growth is the Ras/mitogen activated protein (MAP) kinase signaling cascade. Since the enzymatic functions of the signaling partners are well characterized, this pathway offers many potential “druggable” candidates including Braf, Mek and Ras itself. In this review, we describe this pathway in the context of melanoma tumorigenesis and discuss some of the current relevant pharmacologic treatments and clinical trials.

Keywords: malignant melanoma, therapeutics, chemotherapy, RAS, MAP kinase

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